Pharmaceutical composition

Abstract

Pharmaceutical composition which comprises an insulin sensitivity enhancer in combination with other antidiabetics differing from the enhancer in the mechanism of action, which shows a potent depressive effect on diabetic hyperglycemia and is useful for prophylaxis and treatment of diabetes.

1. A method for treating circulatory disorders in a mammal in need thereof, which comprises administering to said mammal a therapeutically effective amount of an insulin sensitivity enhancer in combination with a biguanide, wherein the insulin sensitivity enhancer is a compound represented by the formula: 
                 
 
       wherein R represents an optionally substituted hydrocarbon or heterocyclic group; Y represents a group represented by —CO—, —CH(OH)— or —NR 3 — wherein R 3  represents an optionally substituted alkyl group; m is 0 or 1; n is 0, 1 or 2; X represents CH or N; A represents a bond or a C 1-7  divalent aliphatic hydrocarbon group; Q represents oxygen atom or sulfur atom; R 1  represents hydrogen atom or an alkyl group; ring E may optionally have 1 to 4 further substituents, and the substituents may optionally be combined with R 1  to form a ring; L and M respectively represent hydrogen atom, or L and M may optionally be combined with each other to form a bond; or a pharmacologically acceptable salt thereof. 
     
     
       2. The method according to  claim 1 , wherein R is an optionally substituted heterocyclic group. 
     
     
       3. The method according to  claim 1 , wherein m is 0. 
     
     
       4. The method according to  claim 1 , wherein X is CH. 
     
     
       5. The method according to  claim 1 , wherein R 1  is hydrogen atom. 
     
     
       6. The method according to  claim 1 , wherein the partial formula: 
                 
 
       wherein R 2  represents hydrogen atom, an alkyl group, an optionally substituted hydroxyl group, a halogen atom, an optionally substituted acyl group, nitro group or an optionally substituted amino group. 
     
     
       7. The method according to  claim 1 , wherein L and M are hydrogen atoms. 
     
     
       8. The method according to  claim 1 , wherein R is pyridyl, oxazolyl or thiazolyl group optionally having 1 to 3 substituents selected from C 1-3  alkyl, furyl, thienyl, phenyl and naphthyl; m is 0; n is 0 or 1; X is CH; A is a bond or —(CH 2 ) 2 —; R 1  is hydrogen atom, wherein the partial formula: 
                 
 
       and wherein R 2  is hydrogen atom or C 1-4  alkoxy group; and L and M are both hydrogen atoms. 
     
     
       9. The method according to  claim 1 , wherein the insulin sensitivity enhancer is pioglitazone or its hydrochloride. 
     
     
       10. The method according to  claim 1 , wherein the biguanide is selected from the group consisting of phenformin, metformin and buformin. 
     
     
       11. The method according to  claim 1 , wherein the biguanide is metformin. 
     
     
       12. The method according to  claim 1 , wherein the insulin sensitivity enhancer is pioglitazone or its hydrochloride and the biguanide is metformin. 
     
     
       13. The method according to  claim 1 , wherein the insulin sensitivity enhancer is 5-[[4-[2-(methyl-2-pyridylamino)ethoxy]phenyl]-methyl]-2,4-thiazolidinedione or its pharmacologically acceptable salt. 
     
     
       14. The method according to  claim 1 , wherein the insulin sensitivity enhancer and biguanide are mixed together to form an admixture and the admixture is administered to the mammal. 
     
     
       15. The method according to  claim 1 , wherein the insulin sensitivity enhancer and biguanide are not mixed together but are administered independently to the mammal.